INTRODUCTION: Ectopic varices are unusual and can involve any site along the GI tract. Only 5% of variceal bleeding is related to ectopic varices such as duodenal varices. Ectopic variceal bleeding is usually massive, difficult to treat, and associated with high mortality rates. High clinical suspicion is warranted. No standardized treatment is recommended, and the management remains challenging with limited success in controlling recurrent bleeding. EUS-guided therapy has evolved as an effective therapeutic modality in gastric varices and this case demonstrates the role of EUS-guided coil embolization (EUS-CE) with cyanoacrylate (CYA) injection in the management of duodenal variceal bleeding. CASE DESCRIPTION/METHODS: 81-year-old female with history of Diffuse large B cell lymphoma on chemotherapy presented with intermittent massive upper gastrointestinal bleeding. CT abdomen showed cirrhotic liver and portal vein thrombosis due to lymphoma involvement. Three endoscopies performed over a period of 5 days revealed 1 cm non-bleeding duodenal ulcer at the duodenal sweep without stigmata of recent bleeding. Due to recurrent bleeding, empiric coil embolization of the gastroduodenal artery and multiple duodenal branches through angiography was done by interventional radiology. However, severe bleeding recurred after the embolization, and the fourth urgent EGD showed large subepithelial violaceous lesions next to the deep penetrating ulcer, highly suspicious for duodenal varices. EGD-EUS confirmed these lesions were duodenal varices. By the fifth day of admission, patient had required 8 units of PRBC. Therefore, the decision was made to treat with EUS-CE. Two coils of 8 and 9 mm were deployed into the larger varix through a 19G EUS-FNA needle followed by 2 ml injection of CYA. A third 6 mm coil was also deployed in the feeder vessel also followed by CYA. Both lead to embolization and cessation of blood flow as demonstrated through Doppler investigation at the end of the procedure. Bleeding stopped and patient was discharged home to complete chemotherapy. DISCUSSION: Bleeding from duodenal varices require high suspicion as vessels could be miss if collapsed soon after bleeding. High clinical suspicion can result in early angiographic evaluation and intervention. Ideal management of ectopic variceal bleeding is still unclear. Multiple endoscopic technique modalities have been reported. EUS-CE with or without CYA injection is a safe endoscopic technique with effective variceal obliteration in most cases.